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Title: Subclonal diversification of primary breast cancer revealed by multiregion sequencing

Abstract

Sequencing cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and late in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer.

Authors:
 [1]; ORCiD logo [2];  [3];  [4];  [2];  [5];  [6];  [7];  [4];  [2];  [2];  [2];  [2];  [6];  [8];  [2];  [2];  [2];  [2];  [2] more »;  [2]; ORCiD logo [2];  [2];  [2];  [2];  [9];  [4];  [9];  [4];  [9];  [4];  [4];  [2];  [4];  [10];  [3];  [2];  [2] « less
  1. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Univ. of Cambridge, Cambridge (United Kingdom)
  2. Wellcome Trust Sanger Institute, Hinxton (United Kingdom)
  3. Univ. of Bergen, Bergen (Norway); Haukeland Univ. Hospital, Bergen (Norway)
  4. Univ. Libre de Bruxelles, Brussels (Belgium)
  5. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Univ. of Leuven, Leuven (Belgium)
  6. Haukeland Univ. Hospital, Bergen (Norway)
  7. Wellcome Trust Sanger Institute, Hinxton (United Kingdom); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  8. Haukeland Univ. Hospital, Bergen (Norway); Univ. of Bergen, Bergen (Norway)
  9. Dana-Farber Cancer Institute, Boston, MA (United States)
  10. Dana-Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1236604
Report Number(s):
LA-UR-14-28200
Journal ID: ISSN 1078-8956; nm.3886
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Medicine
Additional Journal Information:
Journal Volume: 21; Journal Issue: 7; Journal ID: ISSN 1078-8956
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; breast cancer; cancer genomics; cell migration; evolutionary genetics

Citation Formats

Yates, Lucy R., Gerstung, Moritz, Knappskog, Stian, Desmedt, Christine, Gundem, Gunes, Van Loo, Peter, Aas, Turid, Alexandrov, Ludmil B., Larsimont, Denis, Davies, Helen, Li, Yilong, Ju, Young Seok, Ramakrishna, Manasa, Haugland, Hans Kristian, Lilleng, Peer Kaare, Nik-Zainal, Serena, McLaren, Stuart, Butler, Adam, Martin, Sancha, Glodzik, Dominic, Menzies, Andrew, Raine, Keiran, Hinton, Jonathan, Jones, David, Mudie, Laura J., Jiang, Bing, Vincent, Delphine, Greene-Colozzi, April, Adnet, Pierre -Yves, Fatima, Aquila, Maetens, Marion, Ignatiadis, Michail, Stratton, Michael R., Sotiriou, Christos, Richardson, Andrea L., Lønning, Per Eystein, Wedge, David C., and Campbell, Peter J. Subclonal diversification of primary breast cancer revealed by multiregion sequencing. United States: N. p., 2015. Web. doi:10.1038/nm.3886.
Yates, Lucy R., Gerstung, Moritz, Knappskog, Stian, Desmedt, Christine, Gundem, Gunes, Van Loo, Peter, Aas, Turid, Alexandrov, Ludmil B., Larsimont, Denis, Davies, Helen, Li, Yilong, Ju, Young Seok, Ramakrishna, Manasa, Haugland, Hans Kristian, Lilleng, Peer Kaare, Nik-Zainal, Serena, McLaren, Stuart, Butler, Adam, Martin, Sancha, Glodzik, Dominic, Menzies, Andrew, Raine, Keiran, Hinton, Jonathan, Jones, David, Mudie, Laura J., Jiang, Bing, Vincent, Delphine, Greene-Colozzi, April, Adnet, Pierre -Yves, Fatima, Aquila, Maetens, Marion, Ignatiadis, Michail, Stratton, Michael R., Sotiriou, Christos, Richardson, Andrea L., Lønning, Per Eystein, Wedge, David C., & Campbell, Peter J. Subclonal diversification of primary breast cancer revealed by multiregion sequencing. United States. https://doi.org/10.1038/nm.3886
Yates, Lucy R., Gerstung, Moritz, Knappskog, Stian, Desmedt, Christine, Gundem, Gunes, Van Loo, Peter, Aas, Turid, Alexandrov, Ludmil B., Larsimont, Denis, Davies, Helen, Li, Yilong, Ju, Young Seok, Ramakrishna, Manasa, Haugland, Hans Kristian, Lilleng, Peer Kaare, Nik-Zainal, Serena, McLaren, Stuart, Butler, Adam, Martin, Sancha, Glodzik, Dominic, Menzies, Andrew, Raine, Keiran, Hinton, Jonathan, Jones, David, Mudie, Laura J., Jiang, Bing, Vincent, Delphine, Greene-Colozzi, April, Adnet, Pierre -Yves, Fatima, Aquila, Maetens, Marion, Ignatiadis, Michail, Stratton, Michael R., Sotiriou, Christos, Richardson, Andrea L., Lønning, Per Eystein, Wedge, David C., and Campbell, Peter J. 2015. "Subclonal diversification of primary breast cancer revealed by multiregion sequencing". United States. https://doi.org/10.1038/nm.3886. https://www.osti.gov/servlets/purl/1236604.
@article{osti_1236604,
title = {Subclonal diversification of primary breast cancer revealed by multiregion sequencing},
author = {Yates, Lucy R. and Gerstung, Moritz and Knappskog, Stian and Desmedt, Christine and Gundem, Gunes and Van Loo, Peter and Aas, Turid and Alexandrov, Ludmil B. and Larsimont, Denis and Davies, Helen and Li, Yilong and Ju, Young Seok and Ramakrishna, Manasa and Haugland, Hans Kristian and Lilleng, Peer Kaare and Nik-Zainal, Serena and McLaren, Stuart and Butler, Adam and Martin, Sancha and Glodzik, Dominic and Menzies, Andrew and Raine, Keiran and Hinton, Jonathan and Jones, David and Mudie, Laura J. and Jiang, Bing and Vincent, Delphine and Greene-Colozzi, April and Adnet, Pierre -Yves and Fatima, Aquila and Maetens, Marion and Ignatiadis, Michail and Stratton, Michael R. and Sotiriou, Christos and Richardson, Andrea L. and Lønning, Per Eystein and Wedge, David C. and Campbell, Peter J.},
abstractNote = {Sequencing cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and late in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer.},
doi = {10.1038/nm.3886},
url = {https://www.osti.gov/biblio/1236604}, journal = {Nature Medicine},
issn = {1078-8956},
number = 7,
volume = 21,
place = {United States},
year = {Mon Jun 22 00:00:00 EDT 2015},
month = {Mon Jun 22 00:00:00 EDT 2015}
}

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Cited by: 539 works
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Works referenced in this record:

The Life History of 21 Breast Cancers
journal, May 2012


Tumour evolution inferred by single-cell sequencing
journal, March 2011


The clonal and mutational evolution spectrum of primary triple-negative breast cancers
journal, April 2012


Concordance of Genomic Alterations between Primary and Recurrent Breast Cancer
journal, March 2014


Genome remodelling in a basal-like breast cancer metastasis and xenograft
journal, April 2010


Clonal evolution in breast cancer revealed by single nucleus genome sequencing
journal, July 2014


Implementing personalized cancer genomics in clinical trials
journal, April 2013


APC mutations occur early during colorectal tumorigenesis
journal, September 1992


Clinical and biological implications of driver mutations in myelodysplastic syndromes
journal, November 2013


Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma
journal, February 2013


Evolution and dynamics of pancreatic cancer progression
journal, February 2013


A Big Bang model of human colorectal tumor growth
journal, February 2015


Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing
journal, February 2014


Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
journal, March 2012


Distant metastasis occurs late during the genetic evolution of pancreatic cancer
journal, October 2010


A census of amplified and overexpressed human cancer genes
journal, January 2010


The landscape of somatic copy-number alteration across human cancers
journal, February 2010


A census of human cancer genes
journal, March 2004


Discovery and saturation analysis of cancer genes across 21 tumour types
journal, January 2014


IntOGen-mutations identifies cancer drivers across tumor types
journal, September 2013


The landscape of cancer genes and mutational processes in breast cancer
journal, May 2012


Whole-genome analysis informs breast cancer response to aromatase inhibition
journal, June 2012


Sequence analysis of mutations and translocations across breast cancer subtypes
journal, June 2012


Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing
journal, October 2014


Allele-specific copy number analysis of tumors
journal, September 2010


Pan-cancer patterns of somatic copy number alteration
journal, September 2013


The evolutionary history of lethal metastatic prostate cancer
journal, April 2015


Spatial and temporal diversity in genomic instability processes defines lung cancer evolution
journal, October 2014


Genome-driven integrated classification of breast cancer validated in over 7,500 samples
journal, August 2014


Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
journal, September 2001


Molecular portraits of human breast tumours
journal, August 2000


Assessing the clinical utility of cancer genomic and proteomic data across tumor types
journal, June 2014


Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer
journal, January 2010


Heterogeneity of genomic evolution and mutational profiles in multiple myeloma
journal, January 2014


Fast and accurate long-read alignment with Burrows–Wheeler transform
journal, January 2010


Synonymous Mutations Frequently Act as Driver Mutations in Human Cancers
journal, March 2014


High-Definition Reconstruction of Clonal Composition in Cancer
journal, June 2014


THetA: inferring intra-tumor heterogeneity from high-throughput DNA sequencing data
journal, January 2013


Deciphering Signatures of Mutational Processes Operative in Human Cancer
journal, January 2013


Allele-specific copy number analysis of tumors
text, January 2010


Molecular portraits of human breast tumours
text, January 2000


The life history of 21 breast cancers.
journalarticle, January 2012


The Life History of 21 Breast Cancers
journal, August 2015


American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer
journal, June 2010


The evolutionary history of lethal metastatic prostate cancer
text, January 2015


Heterogeneity of genomic evolution and mutational profiles in multiple myeloma.
text, January 2014


The Life History of 21 Breast Cancers
journal, May 2012


High-Definition Reconstruction of Clonal Composition in Cancer
journal, June 2014


Distant metastasis occurs late during the genetic evolution of pancreatic cancer
journal, October 2010


Tumour evolution inferred by single-cell sequencing
journal, March 2011


The clonal and mutational evolution spectrum of primary triple-negative breast cancers
journal, April 2012


The landscape of cancer genes and mutational processes in breast cancer
journal, May 2012


Clonal evolution in breast cancer revealed by single nucleus genome sequencing
journal, July 2014


The evolutionary history of lethal metastatic prostate cancer
journal, April 2015


Assessing the clinical utility of cancer genomic and proteomic data across tumor types
journal, June 2014


Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
journal, September 2001


Genetic and Phenotypic Diversity in Breast Tumor Metastases
journal, January 2014


CCR 20th Anniversary Commentary: The Development of Breast Cancer Molecular Subtyping
journal, April 2015


Who's driving anyway? Herculean efforts to identify the drivers of breast cancer
journal, October 2012


THetA: inferring intra-tumor heterogeneity from high-throughput DNA sequencing data
journal, January 2013


Designing Transformative Clinical Trials in the Cancer Genome Era
journal, May 2013


Molecular portraits of human breast tumours
text, January 2000


Bioconductor : open software development for computational biology and bioinformatics
text, January 2004


Works referencing / citing this record:

Progress in the clinical detection of heterogeneity in breast cancer
journal, October 2016


Aneuploidy: Cancer strength or vulnerability?: Aneuploidy: Cancer strength or vulnerability?
journal, October 2018


Dynamic genome and transcriptional network‐based biomarkers and drugs: precision in breast cancer therapy
journal, November 2018


Genome evolution in ductal carcinoma in situ : invasion of the clones: DCIS genome evolution
journal, November 2016


Breast Cancer Heterogeneity: Roles in Tumorigenesis and Therapeutic Implications
journal, February 2017


The Translational Status of Cancer Liquid Biopsies
journal, November 2019


Spatial and temporal clonal evolution during development of metastatic urothelial carcinoma
journal, August 2016


Intra-tumor heterogeneity of cancer cells and its implications for cancer treatment
journal, September 2015


Changing molecular profile of brain metastases compared with matched breast primary cancers and impact on clinical outcomes
journal, February 2016


Analysis of cancer genomes reveals basic features of human aging and its role in cancer development
journal, August 2016


Reconstructing metastatic seeding patterns of human cancers
journal, January 2017


Punctuated copy number evolution and clonal stasis in triple-negative breast cancer
journal, August 2016


Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer
journal, January 2017


HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
journal, March 2017


Liquid biopsies come of age: towards implementation of circulating tumour DNA
journal, February 2017


The evolution of tumour phylogenetics: principles and practice
journal, February 2017


Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations
journal, March 2018


Abiraterone shows alternate activity in models of endocrine resistant and sensitive disease
journal, July 2018


Ductal carcinoma in situ: to treat or not to treat, that is the question
journal, July 2019


Genomic profiling of multiple breast cancer reveals inter-lesional heterogeneity
journal, January 2020


Cell-free DNA analysis in healthy individuals by next-generation sequencing: a proof of concept and technical validation study
journal, July 2019


A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer
journal, July 2018


Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq
journal, September 2018


Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy
journal, February 2019


Myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia
journal, November 2019


An analysis of genetic heterogeneity in untreated cancers
journal, August 2019


Resolving genetic heterogeneity in cancer
journal, March 2019


Intra-tumour diversification in colorectal cancer at the single-cell level
journal, April 2018


The evolutionary history of 2,658 cancers
journal, February 2020


A community effort to create standards for evaluating tumor subclonal reconstruction
journal, January 2020


Enhancer mapping uncovers phenotypic heterogeneity and evolution in patients with luminal breast cancer
journal, July 2018


A role for chromatin regulatory dynamics in breast cancer evolution
journal, September 2018


Detecting repeated cancer evolution from multi-region tumor sequencing data
journal, August 2018


High-resolution deconstruction of evolution induced by chemotherapy treatments in breast cancer xenografts
journal, December 2018


An Innovative Platform Merging Elemental Analysis and Ftir Imaging for Breast Tissue Analysis
journal, July 2019


ctDNA detected by ddPCR reveals changes in tumour load in metastatic malignant melanoma treated with bevacizumab
journal, November 2019


Designing highly crystalline multifunctional multicolor-luminescence nanosystem for tracking breast cancer heterogeneity
journal, January 2019


Breast tumour organoids: promising models for the genomic and functional characterisation of breast cancer
journal, January 2019


Meltos: multi-sample tumor phylogeny reconstruction for structural variants
journal, October 2019


Whole-genome sequencing of human malignant mesothelioma tumours and cell lines
journal, April 2019


Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas
journal, June 2015


Intratumor Heterogeneity and Circulating Tumor Cell Clusters
journal, June 2017


Single-cell Map of Diverse Immune Phenotypes Driven by the Tumor Microenvironment
posted_content, April 2018


Creating Standards for Evaluating Tumour Subclonal Reconstruction
posted_content, May 2019


Unraveling Tumor-Immune Heterogeneity in Advanced Ovarian Cancer Uncovers Immunogenic Effect of Chemotherapy
posted_content, October 2018


Accuracy of somatic variant detection in multiregional tumor sequencing data
posted_content, May 2019


Spatial Heterogeneity in the Tumor Microenvironment
journal, August 2016


Principles of Reconstructing the Subclonal Architecture of Cancers
journal, March 2017


Order Matters: The Order of Somatic Mutations Influences Cancer Evolution
journal, January 2017


The Cellular Origin and Evolution of Breast Cancer
journal, January 2017


Chromosomal Instability as a Driver of Tumor Heterogeneity and Evolution
journal, February 2017


MiR‐1285‐5p/ TMEM194A axis affects cell proliferation in breast cancer
journal, January 2020


Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state
journal, April 2019


Coexisting genomic aberrations associated with lymph node metastasis in breast cancer
journal, April 2018


Application and optimization of minimally invasive cell-free DNA techniques in oncogenomics
journal, February 2018


Clonal interference of signaling mutations worsens prognosis in core-binding factor acute myeloid leukemia
journal, July 2018


Detailed simulation of cancer exome sequencing data reveals differences and common limitations of variant callers
journal, January 2017


Detecting virus integration sites based on multiple related sequencing data by VirTect
journal, January 2019


Profiling molecular regulators of recurrence in chemorefractory triple-negative breast cancers
journal, August 2019


SiFit: inferring tumor trees from single-cell sequencing data under finite-sites models
journal, September 2017


Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology–Genomic Integration Analysis
journal, February 2016


Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases
journal, December 2016


A sequential Monte Carlo algorithm for inference of subclonal structure in cancer
journal, January 2019


Multicentric breast cancer with heterogeneous histopathology: a multidisciplinary review
journal, February 2020


Novel and Alternative Targets Against Breast Cancer Stemness to Combat Chemoresistance
journal, October 2019


Targeting of the Eukaryotic Translation Initiation Factor 4A Against Breast Cancer Stemness
journal, December 2019


A Tyrosine Kinase Expression Signature Predicts the Post-Operative Clinical Outcome in Triple Negative Breast Cancers
journal, August 2019


A field guide for cancer diagnostics using cell-free DNA: From principles to practice and clinical applications
journal, December 2017


Can conventional DWI accurately assess the size of endometrial cancer?
journal, September 2019


Co-mutation of TP53 and PIK3CA in residual disease after neoadjuvant chemotherapy is associated with poor survival in breast cancer
journal, February 2019


Mutant p53 in breast cancer: potential as a therapeutic target and biomarker
journal, March 2018


Genomic landscape of ductal carcinoma in situ and association with progression
journal, August 2019


A Comparison Between Full-COLD PCR/HRM and PCR Sequencing for Detection of Mutations in Exon 9 of PIK3CA in Breast Cancer Patients
journal, August 2018


Clock-like mutational processes in human somatic cells
journal, November 2015


Somatic mosaicism: on the road to cancer
journal, December 2015


Percolation transition of cooperative mutational effects in colorectal tumorigenesis
journal, November 2017


Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution
journal, January 2018


Genomic patterns of progression in smoldering multiple myeloma
journal, August 2018


High-resolution clonal mapping of multi-organ metastasis in triple negative breast cancer
journal, November 2018


Tumour heterogeneity and metastasis at single-cell resolution
journal, November 2018


Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids
journal, April 2019


A clonal expression biomarker associates with lung cancer mortality
journal, October 2019


Influence of p53 Isoform Expression on Survival in High-Grade Serous Ovarian Cancers
journal, March 2019


Ethnicity-Dependent and -Independent Heterogeneity in Healthy Normal Breast Hierarchy Impacts Tumor Characterization
journal, August 2015


Spatial mutation patterns as markers of early colorectal tumor cell mobility
journal, May 2018


Cancer Target Gene Screening: a web application for breast cancer target gene screening using multi-omics data analysis
journal, January 2019


Intratumor heterogeneity predicts metastasis of triple-negative breast cancer
journal, July 2017


CancerTracer: a curated database for intrapatient tumor heterogeneity
journal, November 2019


Share, but unequally: a plausible mechanism for emergence and maintenance of intratumour heterogeneity
journal, January 2019


The Role of Aneuploidy in Cancer Evolution
journal, October 2016


Metastasis as an evolutionary process
journal, April 2016


Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer
journal, February 2018


Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling
journal, November 2017


Systematic evaluation of immune regulation and modulation
journal, March 2017


Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases
text, January 2016


Liquid biopsies come of age: towards implementation of circulating tumour DNA
text, January 2017


Tumor Heterogeneity, Single-Cell Sequencing, and Drug Resistance
journal, June 2016


A sequential Monte Carlo algorithm for inference of subclonal structure in cancer
text, January 2019


The genomic imprint of cancer therapies helps timing the formation of metastases
journal, February 2019


Is DCIS Overrated?
book, January 2018


Intratumoral Heterogeneity in Ductal Carcinoma In Situ: Chaos and Consequence
journal, September 2018


Finding cancer driver mutations in the era of big data research
journal, April 2018


Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence
journal, September 2017


Translating neoadjuvant therapy into survival benefits: one size does not fit all
journal, March 2016


Targeting the PI3K pathway in cancer: are we making headway?
journal, March 2018


Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer
journal, March 2018


Somatic Trp53 mutations differentially drive breast cancer and evolution of metastases
journal, September 2018


Genomic landscape and chronological reconstruction of driver events in multiple myeloma
journal, August 2019


Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig
journal, February 2020


Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks
journal, October 2016


Liquid biopsy in breast cancer: A comprehensive review
journal, February 2019


The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer
journal, October 2016


Somatic evolutionary timings of driver mutations
journal, January 2018


CCNE1 amplification is associated with poor prognosis in patients with triple negative breast cancer
journal, January 2019


Intra-tumour diversification in colorectal cancer at the single-cell level.
text, January 2018


Multicentric breast cancer with heterogeneous histopathology: a multidisciplinary review
text, January 2020


Overview on Clinical Relevance of Intra-Tumor Heterogeneity
journal, April 2018


Cancer Diagnosis Using a Liquid Biopsy: Challenges and Expectations
text, January 2018


Cancer evolution and heterogeneity
journal, July 2018


Spatiotemporal genomic architecture informs precision oncology in glioblastoma
journal, March 2017


Leukaemia 'firsts' in cancer research and treatment
journal, February 2016


Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer
journal, February 2019


Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy
journal, September 2018


Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma
journal, January 2020


Intra-tumor heterogeneity and clonal exclusivity in renal cell carcinoma
posted_content, April 2018


Single-cell sequencing data reveal widespread recurrence and loss of mutational hits in the life histories of tumors
journal, October 2017


Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling
journal, February 2018


Somatic mutation in cancer and normal cells
journal, September 2015


Learning mutational graphs of individual tumour evolution from single-cell and multi-region sequencing data
journal, April 2019


Multi-region and single-cell sequencing reveal variable genomic heterogeneity in rectal cancer
journal, November 2017


Multicentric breast cancer with heterogeneous histopathology: a multidisciplinary review
text, January 2020


Cancer Diagnosis Using a Liquid Biopsy: Challenges and Expectations
journal, May 2018


Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study
journal, October 2017


On measuring selection in cancer from subclonal mutation frequencies
journal, September 2019


Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy.
text, January 2019


Using State Space Exploration to Determine How Gene Regulatory Networks Constrain Mutation Order in Cancer Evolution
text, January 2019


HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures.
text, January 2017


How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases
journal, December 2019


Cancer cells exhibit clonal diversity in phenotypic plasticity
journal, February 2017


On measuring selection in cancer from subclonal mutation frequencies
posted_content, January 2019


PIPELINEs: Creating Comparable Clinical Knowledge Efficiently by Linking Trial Platforms
journal, October 2016


BCL9L Dysfunction Impairs Caspase-2 Expression Permitting Aneuploidy Tolerance in Colorectal Cancer
journal, January 2017


Genomic Evolution of Breast Cancer Metastasis and Relapse
journal, August 2017


The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer
journal, May 2019


Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis
journal, September 2019


Genetic heterogeneity and clonal evolution during metastasis in breast cancer patient-derived tumor xenograft models
journal, January 2020


ESR1 mutations: Moving towards guiding treatment decision-making in metastatic breast cancer patients
journal, January 2017


Pre-analytics and tumor heterogeneity
journal, March 2020


Multiregional Tumor Trees Are Not Phylogenies
journal, August 2017


Intra-tumor heterogeneity of cancer cells and its implications for cancer treatment
journal, September 2015


Cotargeting of CYP-19 (aromatase) and emerging, pivotal signalling pathways in metastatic breast cancer
journal, December 2016


Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation
journal, November 2016


Punctuated copy number evolution and clonal stasis in triple-negative breast cancer
journal, August 2016


Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples
journal, February 2017


Cell-free DNA analysis in healthy individuals by next-generation sequencing: a proof of concept and technical validation study
journal, July 2019


Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer
journal, October 2017


Percolation transition of cooperative mutational effects in colorectal tumorigenesis
journal, November 2017


Combating subclonal evolution of resistant cancer phenotypes
journal, November 2017


Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy
journal, February 2019


Genomic landscape and chronological reconstruction of driver events in multiple myeloma
journal, August 2019


Myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia
journal, November 2019


A community effort to create standards for evaluating tumor subclonal reconstruction
journal, January 2020


High-resolution deconstruction of evolution induced by chemotherapy treatments in breast cancer xenografts
journal, December 2018


An Innovative Platform Merging Elemental Analysis and Ftir Imaging for Breast Tissue Analysis
journal, July 2019


Ethnicity-Dependent and -Independent Heterogeneity in Healthy Normal Breast Hierarchy Impacts Tumor Characterization
journal, August 2015


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journal, May 2019


Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks
journal, October 2016


Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer
journal, February 2016


Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling
journal, February 2018


MiR‐1285‐5p/ TMEM194A axis affects cell proliferation in breast cancer
journal, January 2020


The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer
journal, October 2016


Measuring Clonal Evolution in Cancer with Genomics
journal, August 2019


Mutation Profiling of Key Cancer Genes in Primary Breast Cancers and Their Distant Metastases
journal, June 2018


CCNE1 amplification is associated with poor prognosis in patients with triple negative breast cancer
journal, January 2019


SiFit: inferring tumor trees from single-cell sequencing data under finite-sites models
journal, September 2017


Translating insights into tumor evolution to clinical practice: promises and challenges
journal, March 2019


Phylogeny-based tumor subclone identification using a Bayesian feature allocation model
journal, June 2019


Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases
journal, December 2016


Constitutional Mosaic Epimutations – a hidden cause of cancer?
journal, April 2019


Epigenetic determinants of metastasis.
journalarticle, January 2017


Intratumoral heterogeneity of intrahepatic cholangiocarcinoma
journal, January 2017


Diversity index as a novel prognostic factor in breast cancer
journal, September 2017


Investigation of appropriate pre-analytical procedure for circulating free DNA from liquid biopsy
journal, August 2018


Pan-cancer analysis of intratumor heterogeneity as a prognostic determinant of survival
journal, January 2016


Overview on Clinical Relevance of Intra-Tumor Heterogeneity
journal, April 2018


Novel and Alternative Targets Against Breast Cancer Stemness to Combat Chemoresistance
journal, October 2019


A Tyrosine Kinase Expression Signature Predicts the Post-Operative Clinical Outcome in Triple Negative Breast Cancers
journal, August 2019


How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases
journal, December 2019


Targeted sequencing reveals genetic variants associated with sensitivity of 79 human cancer xenografts to anticancer drugs
journal, November 2017


Cancer Bioinformatic Methods to Infer Meaningful Data from Small-Size Cohorts
journal, January 2015